This research project proposes to use lithium (7Li) Magnetic Resonance Spectroscopy (MRS) to measure brain lithium levels in children and adolescents with Bipolar I Disorder (BPD) who are being treated with the medication. Lithium is considered to be a first-line mood stabilizer for acute mania, hypomania, depression, and prevention of relapse in youth. However, lithium has not been adequately studied in pediatric BPD samples; this shortcoming is currently being addressed through a multi-site contract with NIH [Collaborative Lithium Trials (COLT)]. We plan to measure brain lithium levels in a subgroup of patients participating in the COLT study. This study will be the first to evaluate the clinical significance of brain lithium levels in youths. Subjects enrolled in a COLT protocol (8-week double-blind placebo-controlled trial of lithium) at the Harvard site (expected N=25, ages 7 to 17 years old, with DSM-IV-TR diagnosis of Bipolar I Disorder, manic or mixed phase) will be invited to participate in this neuroimaging study. In order to ensure that participants remain blind to their drug status, all subjects will undergo 7Li MRS at weeks 2 and 8 of the efficacy trial. In addition, we will acquire proton (1H) MRS from the anterior cingulate cortex (ACC) at baseline and at 2 and 8 weeks to obtain measurements of myo-Inositol (Ino). All MRS examinations will be performed on 4.0 Tesla Varian/Inova. scanner. Serum lithium levels, YMRS, and Clinical Global Impression (CGI) will be obtained prior to the scan. Side effects will be measured using the Side Effects Form for Children and Adolescents and the UKU Side Effect Rating Scale. The goals of this project are to: 1) Use 7Li MRS to obtain the brain-to-serum lithium ratio in children and adolescents to further define the serum lithium therapeutic range necessary to achieve lithium treatment response in an age dependent manner. 2) Use 7Li MRS to obtain the brain-to-serum lithium ratio in children and adolescents to further examine the serum lithium therapeutic range to minimize treatment emergent side effects in an age-dependent manner. 3) Use 1H MRS to examine the myo-Inositol depletion hypothesis of lithium efficacy in pediatric BPD. Our underlying hypothesis is that the brain-to-serum lithium ratio will increase with age. In addition, we hypothesize that higher Ino levels will be associated with mania, and positive responses to lithium treatment will be accompanied by decreased Ino levels. .Project Narrative: Lithium is considered to be a first-line mood stabilizer for acute mania, hypomania, depression, and prevention of relapse in youth. However, it has not been adequately studied in pediatric samples; this shortcoming is currently being addressed through a multi-site trial under contract with NIH. We propose to use MRI-based methods to measure brain lithium levels in children and adolescents with bipolar disorder who are participating in that trial, making this the first study to evaluate the clinical significance of brain lithium levels in youths with BPD. [unreadable] [unreadable] [unreadable]